Atrial septal defect (ASD) is one of the most frequent congenital heart defects (CHDs) with a variable phenotypic effect depending on the size of the septal shunt. We identified two pedigrees comprising 20 members segregating isolated autosomal dominant secundum ASD. By genetic mapping, we identified the gene-encoding alpha-cardiac actin (ACTC1), which is essential for cardiac contraction, as the likely candidate. A mutation screen of the coding regions of ACTC1 revealed a founder mutation predicting an M123V substitution in affected individuals of both pedigrees. Functional analysis of ACTC1 with an M123V substitution shows a reduced affinity for myosin, but with retained actomyosin motor properties. We also screened 408 sporadic patients with CHDs and identified a case with ASD and a 17-bp deletion in ACTC1 predicting a non-functional protein. Morpholino (MO) knockdown of ACTC1 in chick embryos produces delayed looping and reduced atrial septa, supporting a developmental role for this protein. The combined results indicate, for the first time, that ACTC1 mutations or reduced ACTC1 levels may lead to ASD without signs of cardiomyopathy.

Prophylactic PM treatment is recommended even for symptom-free adults with CCHB because of the high incidence of unpredictable SA attacks with considerable mortality from first attacks, a gradually decreasing VR, significant morbidity, and a high incidence of "acquired" mitral insufficiency.

The pacemaking activity of specialized tissues in the heart and gut results in lifelong rhythmic contractions. Here we describe a new syndrome characterized by Chronic Atrial and Intestinal Dysrhythmia, termed CAID syndrome, in 16 French Canadians and 1 Swede. We show that a single shared homozygous founder mutation in SGOL1, a component of the cohesin complex, causes CAID syndrome. Cultured dermal fibroblasts from affected individuals showed accelerated cell cycle progression, a higher rate of senescence and enhanced activation of TGF-β signaling. Karyotypes showed the typical railroad appearance of a centromeric cohesion defect. Tissues derived from affected individuals displayed pathological changes in both the enteric nervous system and smooth muscle. Morpholino-induced knockdown of sgol1 in zebrafish recapitulated the abnormalities seen in humans with CAID syndrome. Our findings identify CAID syndrome as a novel generalized dysrhythmia, suggesting a new role for SGOL1 and the cohesin complex in mediating the integrity of human cardiac and gut rhythm.

To examine perinatal risk factors for Crohn's disease and ulcerative colitis, the authors analyzed birth records for 257 known case participants delivered from 1924 through 1957 at the University Hospital in Uppsala County, Sweden, and compared them with records for 514 controls delivered at the hospital. The two groups were matched by date of birth, sex, and either maternal age or parity. Eleven study variables were abstracted from standard forms that recorded health events during the pregnancy and the delivery hospitalization. Participants were more likely than controls to have a recorded health event (odds ratio (OR) = 4.4; 95% confidence interval (CI) 3.0-6.4). In a multivariate model, this increased risk was evident for infectious (OR = 3.8; 95% CI 2.6-5.8) and noninfectious (OR = 3.5; 95% CI 2.0-6.3) events. Perinatal health events may have contributed to 40% of the inflammatory bowel disease cases in our study. Infants from families with low socioeconomic status had greater risk of inflammatory bowel disease than did infants from families with high socioeconomic status (OR = 3.0, 95% CI 1.5-6.1). Perinatal health events and low socioeconomic status independently increased the risk of inflammatory bowel disease.

Resuscitation with 100% oxygen immediately postpartum is associated with childhood lymphatic leukaemia, but further studies are warranted to confirm the findings.